The role of immunosuppression in the long-term survival of tracheal allografts.

Abstract

To assess the functional aspects of vascularized tracheal allograft transplant models and the long-term fate of these allografts. To examine the effects of cyclosporin A (CsA), 10 mg/kg per day, on the long-term survival of vascularized tracheal allografts and the presence and significance of host immune tolerance after cessation of immunosuppression. In a rabbit model, tracheal allografts were orthotopically transplanted after an initial period of heterotopic fascia revascularization. A full-thickness skin allograft from the same donor was used as an external monitor of the rejection process. Treatment with CsA was discontinued (group 2) or given intermittently (group 3) after an initial course of continuous CsA administration varying from 2 to 10 weeks. The first group received a continuous regimen of CsA for 10 weeks. Tracheal and skin allograft deterioration, microcirculation of tracheal transplant, mucociliary clearance, and histopathologic examination. Tracheal allografts under continuous immunosuppression with CsA, 10 mg/kg per day, showed no rejection and remained functional with preservation of mucociliary activity. After an initial course of CsA to achieve solid tracheal union, subsequent cessation and intermittent pulsing of the immunosuppressant were insufficient in maintaining indefinite graft survival. Chronic allograft rejection with simultaneous endothelial graft repopulation could be induced by intermittent pulsing of CsA, which led to prolonged allograft survival in some group 3 animals. Continuous immunosuppression is necessary to preserve an optimal morphological and functional condition of tracheal allografts.